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29 Jun 2009
Analyzing High-Resolution Microscopy Images
UC Davis researchers analyzed high-resolution microscopy images of cells during mitosis.
Clicks: 145
Descriptions: 1
19 Jun 2009
Experiments with MATLAB, by Cleve Moler
Online textbook that introduces MATLAB through the use of interesting puzzles and problems
Clicks: 461
Descriptions: 1
19 Jun 2009
Optimization Models in Computational Biology
Graduate course on computational problems in bioinformatics and their applications
Clicks: 203
Descriptions: 1
19 Jun 2009
Introduction to Applied Scientific Computing with MATLAB
Uses MATLAB to introduce topics such as simulation, visualization, statistics, and data processing.
Clicks: 262
Descriptions: 1
19 Jun 2009
Mechanics of Growth
MATLAB course on theoretical and computational models of the biomechanics of growth
Clicks: 136
Descriptions: 1
19 Jun 2009
Numerical Methods with MATLAB: Implementations and Applications
Introduces MATLAB programming and numerical methods; comes MATLAB files and lecture slides.
Clicks: 609
Descriptions: 1
19 Jun 2009
Modeling and Simulation of Natural and Engineered Systems
MATLAB problem sets for teaching stationary processes, linear dynamic systems and neural networks
Clicks: 233
Descriptions: 1
5 Sep 2008
Introduction to Computer Programming for Scientists and Engineers
This course uses MATLAB to introduce the elements of procedural and object-oriented programming. ...
Clicks: 420
Descriptions: 1


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Pac-Man Championship Edition DX+, the title update to the 2010 arcade game, chomps onto various platforms on September 25. CE DX+ commemorates Pac's neon antics coming to Steam as a standalone, but it'll also be available for on PS3, 360, and Windows 8 as a free update to CE DX.
Going by last month's leak, CE DX+ itself provides light enhancments, adding leaderboard tweaks, challenge-based medals, and friend comparisons. As producer Kunito Komori explained to me, comparisons are tied to a specific friend's scores that are displayed on the CE DX+ dashboard, giving players another mark to top in addition to their own.
The more exciting newness is the 'All You Can Eat' DLC that CE DX+ grants access to, comprising four maps, three reskins, and two pieces of background music. The reskins include Rally-X, Dig Dug, and Pac-Man and the Ghostly Adventures; they're cute enough, but the real meat is the four maps.
Gallery | 8 Photos
Pac-Man CE DX+ (TGS 2013)
The new maps look strong, too. Big Eater, as the name suggests, seems more geared towards the regular style of chewing up as many ghosts as possible. Mountain was my favorite, though, placing ghosts in staircase patterns that led me up and down the map, forcing me into sequences of sharp zigzag turns - doing that for five minutes straight can only lead to chaos. It's these extras, adding some variety to the play, that make me want to return to CE DX next week.
Buy from $270
- Key specs
- Reviews • 18
- Prices
- Discussions
- Game format Optical disc, Downloadable
- Online features Multiplayer, Voice chat, Video chat, Store, Browser
- Drive capacity 250 GB
- Controller type Wired, Wireless
- Motion controls Accelerometer, Gyroscopic
- Video outputs HDMI (v1.3), RCA / composite
- Released 2012-09-25
Microsoft Xbox One


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Orange for Animal Cruelty Awareness wants to
STOP the cruelty of Greyhound Racing
Greyhound Racing kills!
Greyhound Racing kills!
Forced arbitration clauses pre-emptively block consumers from going to court if the bank does something wrong.
School choice programs empower more than 308,000 children across the nation, but thousands more don't have any options.
Puppy Doe was brutally tortured and in her memory we want to help animals.
Many animals who are advertised on Craigslist are abused and are sometimes even killed—as a result of these ads.
Sign this petition to pressure the government of Argentina to release Arturo


text:
- An ISBN is the 10 or 13 digit number, usually printed on the back of a book with a bar code, that serves as a unique identifier for the book.
- Searching by ISBN is the best way to search because it will get you the exact title and edition that you need.
- Many professors include the ISBN on their syllabi or in their course management system.
If you don't have the ISBN, try a title or author search.
Title search
- Enter all words in the title you are looking for. The search engine will try to find books that have all the words you entered in the title. Leave out words such as "a," "an," or "the."
- When including edition, use numeric values. For example, "1st edition" instead of "first edition."
Author search
- Enter all or part of the author name you are looking for.
- You do not need to enter a first name, but if there are a lot of books by authors with the same last name, it may help to narrow the results.
- You can enter the name in any order such as "John Smith" or "Smith John." Avoid using a comma since it has a special meaning in the search.
Keyword search
- You can search by keyword but this approach is not recommended as it will likely return a large set of results.
- If you want to search by keyword, try a combination of author and keyword. For example, "Warren Accounting" where "Warren" is the author and "Accounting" is the keyword.
To refine your results, use the filtering/sorting options
- Filter options include product type and discipline area. Sort options include alphabetical sort (ascending or descending) and copyright year (ascending or descending).
Print version includes Resume Generator CD-ROM
AUTHORS: Zedlitz, Robert H. - ©2011
Research, find, and land the job you want with GETTING A JOB: PROCESS KIT, Sixth Edition. You'll learn how to research jobs and companies, look for job leads, respond to job ads effectively, prepare for an interview, and evaluate and accept job offers. The kit includes an employment profile, worksheets, and techniques to boost your confidence and help you obtain employment. You can also save time preparing your resume and keep it updated using the RESUME GENERATOR CD that accompanies the kit. This powerful tool makes it easy to prepare personalized and professional resumes and other employment documents, which you can organize and store in a provided resume cover and employment portfolio. In addition, the CD includes helpful tips on how to develop a winning resume, what type of cover letter to use and when, action words that sell, and other employment documents to help ease the job search process.
CengageBrain offers two types of free content:


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2005 Toyota Prius 4dr Hatchback (1.5L 4cyl gas/electric hybrid CVT)
Got 53 mpg avg. for 8700 miles. Old car got 23. Go figure, literally. At $2.70/gal and 20000 miles annual usage, we're saving $2240/yr. So breakeven time for purchase price difference should be a couple of years. It is also comforting to know that we are killing demand, not people. This in addition to emissions reduction. Isn't this a no brainer for these three reasons?
Gear shift, smart key and spacious "trunk" with fold down seats.
Gas tank redesign so gas nozzle doesn't shut off about 2 gal. short of full. Also would like reverse beeper to sound externally also.
My drive to work is 10 miles - half highway, half city and I have never gotten less then 50mpg. First long trip is 3 weeks off and can't wait to use the cruise control.
Amazing interior space - actually got 10' boards insde with no problem.
The beige interior is tough to keep clean
This vehicle has exceeded my expectations. Fuel economy is better than I expected (52-54 MPG) considering driving in an often hilly terrain. Quiet and smooth ride. Love the tech innovations. The Consumption display has changed how I drive. In a world where we are faced with issues of pollution and global warming, and reliance on fossil fuels and the related political implications of oil influencing our foreign policy, this car is a great alternative for a better world. Therefore, to me it is so worth spending thousands more for a company like Toyota to reward them for all the developmental costs they put into hybrid technology.
Sophisticated display for consumption and energy information. ICE engine stopping at traffic lights, etc. Interior and exterior design.
Perhaps an optional bank of batteries to allow for plugging in to significantly increase mileage toward triple digits.
I've had 17 vehicles so far at the age of 28. From 1967 to 2004 and chevy to toyota this car is quite impressive. At first you may be taken by the overall exterior design, but once you get in this car everything changes. Its like a computer on wheels and has every accessory you'll ever need. The interactive display is amazing with the navigation and integrated phone system. Plus the added bonus of seeing what engine is running and what MPG your getting at any specific point in time while your driving. Its interesting to know that your gas engine is off whenever your coasting, braking, or in stop and go traffic. You have got to test drive this car to get the feel of it.I guarantee you'll buy
navigation, interactive display, keyless entry and operation (leaves keys in your pocket with smart key system) digital dash speedometer, ride quality, gas mileage, reliability rating, interior room (classified as a midsize car)
Exterior design, make rear window one complete window and not two, better sound system(even upgraded system isnt that great)
I've owned a 2005 for only a month. I am still amazed at the technology that Toyota has designed into this car. It's also fun to drive. My second car is a convertible sports car, and I must say that most often, it's difficult deciding which one to take out.
Navigation control system, near heads up display for speedometer.
More adjustments on the drivers seat or telescoping steering wheel.
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Vaser Liposuction
Vaser Liposuction WORTH IT RATING DETAILS
in the last 24 months
in the last 12 months
over all time
- Average Price: $6,150
Reviews from the Community
Vaser 4D Hi-Def Liposuction - Great Results from Dr. Hoyos - Bogota, Colombia
It has been almost two months since my surgery was performed with Dr. Alfredo Hoyos. Not be able to speak Spanish fluently I was a little hesitant on traveling to a foreign country to have plastic surgery performed. (I have heard and seen nightmares on TV/magazines from other doctors) Since it... READ MORE
51 Year Old Male Vaser Liposuction to Chest, Flanks, Abdomen and Inside Knees. Thailand, TH
Due to bad lifestyle choices I found myself in bad physical condition when I hit 50, with the body of a 60 year old and mental vitality in the 30's. Weight at time of surgery was 220 pounds which is 30 pounds overweight. I recently moved from the Middle East to a new work assignment in Thailand... READ MORE
VASER LIPO WITH LAGRASSO ---HE IS THE BEST!!!!! -Miami, FL
Okay people i finally scheduled my lipo of full front abdomen lower and upper and my back i really wanted to a BBL but i dont have the balls. lol, im freaked out already about anesthesia and even just getting a surgery done but im ready to get rid of this gut...anyway has anyone had this done?... READ MORE
Bangkok - Vaser Liposuction with Dr Montien - Thailand, TH
I've written a post on previous liposuction that turned out with results I wasn't very happy with because of the outcome I had to consider further liposuction. Dec 2014 I obtained 2 quotes (I also posted a review on this) one from a cosmetic surgeon who said Vaser can be done (revision) on my... READ MORE
Vaser Of: Upper Arms, Abs, Flanks, Hips, and Sacral (Lower Back) - Bellevue, WA
I am a 32 year old female runner (~20 miles a week) with no kids, 5'4" tall, 140lbs pre-op Depending on the amount of areas treated, Vaser Lipo will result in significant down-time. Immediately following surgery, I was able to walk around, but at granny speed. Now at 3 weeks post-op, I'm... READ MORE
37 Year Old African American Female. Vaser Lipo for Upper and Lower Abs, Anterior and Posterior Flanks - Roswell, GA
I have been over weight almost all my life. I recently lost a lit of weight going from 360 lbs to 263lbs. I am at a very long plateau and need a jolt. This surgery is to help me remove some extra fat that doesn't seem to be going anywhere, and I plan to continue my weight loss journey post... READ MORE
30 Year Old, Mother of One Vaser Lipo, Nu Cosmetics Liverpool
I am both excited and scared about my surgery which is less than 3 months away. Since having a baby my stomach has a full 3d effect and I am very thick from the side. I am a size 16 and I can't wear t shirts, I live in baggy shirts blouses and most recently a corset to hide my big stomach.... READ MORE
Love my new Figure Jacksonville, FL
I am having Vaser Lipo done 12/11/14 with Dr. Patrick Basile at Coastal Cosmetics here in Jacksonville, Fla Initially I was interested in smart lipo due to the fact that I've seen and read so many reviews and videos on the procedure on here and also YouTube and their results were Great But the... READ MORE
Zap That Fat! - Vaser at Riverbanks, UK
Tomorrow's the day! I'll be having vaser liposelection to my upper and lower abdomen and flanks (sides) by Dr Ravi Jain at Riverbanks Clinic in Harpenden, UK. I'm both excited and nervous. Excited because I can't wait to get rid of my horrible, pudgy stomach. Nervous because I am taking a gamble... READ MORE
36YO 136 Lbs 1 Child - Pasadena, CA
Eve before surgery Finding myself obsessing the last week about whether to do this or not... Money is paid, going forward The plan is for vaser liposuction on upper, mid and lower abdomen, flanks. For thighs: outer, inner and anterior as well as knees. If we can do arms and lateral back that... READ MORE
Vaser Hi Def Liposculpture - Sacramento, CA
I am almost one week post op, so I'm not sure of my results yet! I have always had a short torso and was straight up and down so my goal was to hopefully end up with a waistline and some semblance of a figure:). I will write more later but here is the gist: I weigh 127 and I'm 5'3. I went to... READ MORE
New Body Desired - Cherry Hill, NJ
After years of thinking about it, I am finally taking the plunge. On Friday I'll be getting liposuction of inner and outer thighs, upper and lower abs, as well as flanks. I interviewed 2 providers, Dr. Evan Sorokin, and SonoBello. Really liked both places, but chose Dr. Sorokin. Besides being... READ MORE
It Works- Warsaw, Poland
The areas which were liposuctioned were lower and upper abdomen and flanks. The procedure itself was painless as it was done under IV sedation, I woke up a few hours later and I was told I had about 1.5 litres of fat removed. I still had bandages and a drainage tube attached to bag to... READ MORE
35 Years 3 Kids . - California
9 days till I have my thighs done and I'm super nervous. I really don't know what to expect. I'm 5'2 and weigh 150 lbs. I just want to feel good in my own skin. I'm doing this simply for me. Any advise would be so nice... what should i expect after this is done. Will i have alot of down time.... READ MORE
I'm Nervous and Excited at the Same Time - Bangkok, TH
Well it's 5 days until my surgery date. I'm nervous, excited, petrified and happy that I'm finally doing something for me. 5 years ago I was thin, happy and I thought healthy, then I was diagnosed with hashimotos and even though I lived the same healthy lifestyle the weight just kept piling on... READ MORE
Vaser High Def at Selston Cosmetic Clinic, Nottingham, GB
I had often thought about having liposuction but honestly didn't think I would ever be writing a post-surgery blog, Reading about other people's experiences gave me a good insight of what to expect so In writing my own account I hope it helps others make an informed decision about vaser high... READ MORE
Improve Waist to Knees - Spain
Finally I'll have the operation that have been waiting so long! I've always had a pear shape too exaggerated, my thighs are too wide and over the years I have been losing the shape of the waist. I'm 35, have no children and have always taken care of me, but the thigh area has always resisted... READ MORE
Vaser Med-def Touch Up - London
Hey, I'm a 30yo male and go to the gym 4 times a week - like most people who undergo vaser I've been tying to shed stubborn fat around my abs and no matter how hard I try it won't go! I can feel the muscles underneath my flab so have finally decided to get vaser med def after almost 6 months of... READ MORE
37, Sick of Saddle Bags and Mummy Tummy - London, GB
I've always had trouble with my saddle bags, even as a skinny teenager is till had them. I've spent my life covering up the tops of my legs and struggling to find trousers or jeans to fit. And now after two beautiful children I have a lovely mummy tummy too. I'm fairly active, do exercise... READ MORE
20 years old, getting hi def vaser lipo on abdomen and posterior abdomen next month at selston cosmetic clinic. - Nottingham, GB
Hi i'm 20 years old i'm getting vaser liposuction done next month of my abdomen and posterior abdomen next month. I am very anxious and depressed since I was always a chubby girl my whole life. I cant even imagine how would my tummy look like afterwards and will it be ever flat. i sit on real... READ MORE


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Policy Minute: Drone Testing Program Takes Flight, Journalists at Controls
The Increasing Visibility of Driver Health
Potential for Vicarious Liability Under the Graves Amendment
FMCSA's Certified Medical Examiner Mandate to Start on May 21, 2014
Understanding Supplemental Spousal Liability Insurance in NY
PennDOT to Increase Number of Pennsylvania Bridges with Weight Restrictions
Federal Court Upholds Majority of Hours-of-Service Rule
New Jersey to consider allowing police to search cell phones to combat distracted driving
Court Schedules Arguments on FMCSA's New Hours of Service Rule on March 15, 2013
Doing Business In Canada
Who pays for road damage in Pennsylvania after ACT 13?
Marcellus gas fuels Natural Gas Vehicles
Google real estate director John Igoe - San Francisco Construction & Development Summit
Last week, we discussed public reports of an investigation by the DOJ of four major airlines (American, Delta, Southwest, and United) regarding possible collusion. Over the past two months, a number of consumers have filed...more
As food transporters grapple with the myriad of compliance issues raised by the Food Safety Modernization Act and the FDA's looming proposed "Food Safety Rule on the Sanitary Transportation of Human and Animal Food," carriers...more
DOT's Office of Aviation Enforcement and Proceedings issued a notice temporarily amending its enforcement policy regarding airlines' obligation to honor "mistaken fares." Until now, DOT's Enforcement Office has generally...more
Airlines operating in Australia currently face an unprecedented degree of legal and regulatory change. This shifting landscape presents both opportunities and risks. The below table summaries key competition cases in the...more
This past year, we witnessed the GM Ignition Switch investigation, which involved massive recalls, multiple Congressional hearings, and civil penalties; the ongoing Takata airbag inflator investigation and recalls (and more...more
Although the FDA has characterized the risk of food contamination during transportation as "low," a proposed FDA regulation, entitled "Sanitary Transportation of Human and Animal Food" will impose new restrictions which all...more
Airlines offer frequent-flyer programs to reward loyal customers and attract new ones by awarding various perks based on the "miles" each member accumulates. In practice, however, frequent-flyer programs too often attract...more
Last week, Senator Jay Rockefeller (D-W.Va.) sent a letter to the top ten revenue generating passenger airlines in the United States, opening an inquiry into their practices related to charging additional fees for optional...more
Chicago taxis may seem annoying but studies of urban areas show that cabs reduce traffic congestion and allow some city dwellers the luxury of not owning an automobile....more
A recent decision of the Commercial Court in London (handed down on 8 November 2011) has clarified the limits of a ship owner's obligation under the Conwartime 1993 clauses to obey his charterer's orders to navigate waters...more
In This Issue:
US Import Policy; Tariffs and Import Restrictions; Preferential Duty Programs; Country of Origin; Classification; Procedures; Consumer Product Safety; and, Miscellaneous.
Excerpt from "US Import...more
On April 29, 2010, new federal aviation regulations were enacted which govern the protection of passengers when delays occur in airline travel. These regulations, which are...more
No one would deny that moving is a very stressful time in life. Pulling up roots and trying to set up again in a new place is never easy. So imagine how much worse it can be if your movers are responsible for substantial...more
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Egg Desserts
Looking for egg desserts? Find delicious egg desserts including egg white desserts, egg yolk desserts, and more egg desserts and ideas.
Recipe Spotlight
This warm and hearty dessert is perfect on any cold, blustery winter evening. And the slow cooker fills your kitchen with an amazing aroma. My stomach is growling just thinking about it! —Maiah Albi, Carlsbad, CaliforniaView Slow-Cooked Bread Pudding Recipe


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Live: Astros Up 2-0 vs. Yanks in AL Wild Card
CFB Playoff Committee Has a Mess on Its Hands
Top Week 5 Waiver Pickups, Drops
This Isn't the Boogie You're Used To
Week 4 NFL Awards
Woman Says She Cheated with NHL Player
Brady Paid Practice Players for INTs
Deceased Fan Gets Last Laugh on A-Rod
Harden: 'I'm the Best Player in the League'
Legendary RBs Pick Their Modern Clone
Gronk Can't Wait to Play the Cowboys
Pee Wee Players Would Rather 'Nae Nae'
Steph Flashes Obscene Preseason Swag
This MMA Fighter Needs a Diaper
LBJ Delivers Ultimate Dagger in NBA 2K16
Mathieu Hooks Fans Up with Coldstone
Shaq's Sons Are Pretty Good at Dunking
Marbury Says MJ's Shoes Get Kids Killed
J.R. Won't Give Kicks to Warriors Fan
Sorry Kid, Julius Randle Is Tall
Internet Explodes After Botched MNF Call
Welcome to the L.O.B., Megatron
Stephen A. Issues Threat to Durant
Jimmy Thinks Blocking Is Optional
Bennett Interrupts Post-Game: Pay Kam!
The Quick Rise and Faster Fall of 'Big Country'
MLB 300: Top 40 Corner Outfielders
Foreign Phenom Has NBA Scouts Drooling Already
MLB 300: Ranking Top 25 Third Basemen
Minor League Burnouts Don't Become This Good
War Machine's Trial Will Not Be Pretty
Dockett: Mother's Killer 'Is Still Out'
The NBA Elites' Offseason Playground
Wenger Was 'One Loss Away from Quitting'
Malone's Individual Greatness Lifted His Teams
Mets' Harvey Misses Mandatory Workout
OBJ Accused of Punching Bills Players
Report: Aldon Pleads Not Guilty to Charges
Luck: I'm Not Where I Want to Be
Report: Teams Interested in Roddy White
Steve Spurrier's Final Act Is Getting Ugly
Looking for a Sleeper for NBA MVP? Don't Laugh, but It May Be DeMarcus Cousins
Coming to Terms with Daniel Cormier's UFC Title Reign in the Shadow of Jon Jones
NFL Report Cards: Team-by-Team Grades for Week 4
2016 NFL Mock Draft: Matt Miller's Quarter-Season Predictions
Yankee Stadium Security Lines Causing Major Delays
Dodgers Name NLDS Rotation; Kershaw to Start Game 1
Watch: Rasmus Takes Tanaka Deep, Flips Bat
Live: HOU Up 1-0 After Tanaka Escapes Early Trouble
Sabathia, Hamilton and the Road to Redemption
Root for the Yankees in the Playoffs
Puig Might Be a Bench Guy in NLDS
If He Threw Punches, Beckham Jr. Could Be Disciplined
Girardi to Ellsbury: You're Getting into the Game Tonight
Where OBJ Has Most Success in Record-Setting Start


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Saturday, July 25, 2015
Join more than 1,000 other animal advocates and their four-legged friends for Washington's biggest dog walk -- the 25th annual Dog-A-Thon! Held at Fort Steilacoom Park in Lakewood, this fun, family event has something for everyone: lakeside and scenic trails, dozens of pet-related booths, demonstrations, contests, entertainment, food trucks, and much more! Best of all, the walk benefits homeless animals at the Humane Society. Last year, the Dog-A-Thon raised $253,000 for our furry friends, and we need your help to raise even more in 2015.
Start by creating your own personalized web page right here. Let your friends know why you care about animals, add a photo, and send a link to everyone you know. It's the fun, effortless way to support homeless pets!
Every year, the Humane Society for Tacoma & Pierce County is able to find loving homes for more than 6,000 pets, and reunite thousands more with their owners.
With your support, more than 1,300 orphaned, ill, or unsocialized pets are fostered; 3,000 pets are spayed and neutered for low-income owners; and more than 5,000 families receive help feeding their pets through our Emergency Pet Food Bank.
Your Dog-A-Thon pledges also fund medical care, food, shelter, bathing supplies, and many other essentials for shelter pets. We couldn't do it without you!
Thank you for helping animals and giving the most vulnerable among us a second chance at life.
See you at the Dog-A-Thon!
$149,175 raised | 975 supporters
$5,150 raised | 32 supporters
$4,885 raised | 10 supporters
$2,360 raised | 12 supporters
$2,300 raised | 16 supporters
$2,180 raised | 33 supporters
$153,670 raised | 1019 supporters
$5,820 raised | 47 supporters
$2,460 raised | 13 supporters
$2,140 raised | 6 supporters
$2,000 raised | 21 supporters
$1,735 raised | 26 supporters


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She's always a delight to have around, and last night (June 14) Penelope Cruz was spotted at "The Tonight Show with Jay Leno."
The "Vanilla Sky" actress looked amazing in a beautiful black dress as she chatted about her new Woody Allen film "To Rome With Love."
Opening up the annual cinema celebration, the cast of "To Rome with Love" joined together for their movie's Los Angeles Film Festival premiere on Thursday night (June 14).
Held at Regal Cinemas L.A. LIVE Stadium 14, director Woody Allen and wife Soon-Yi Previn were alongside the comedy caper's leading lady Penelope Cruz, as well as co-stars Alison Pill and Greta Gerwig.
Dressing down for their family flight, Penelope Cruz and Javier Bardem were spotted making their way through the Barajas airport with their son, Leo, in Madrid, Spain on Thursday (June 7).
In an all black ensemble, the "Puss and Boots" actress carried her little prince in front of her with the aid of a baby wrap while her 43-year-old actor husband tended to the luggage as he walked a few steps behind.
The film has already created massive buzz with word of its exceptional cast, and Javier Bardemand Ridley Scott's "The Counselor" could be adding yet another A-list name to its roster.
According to The Hollywood Reporter, Bardem's bombshell wife, Penelope Cruz is in talks to join the highly-antcipated drama.
After tending to a morning photo call earlier in the day, the cast of "To Rome with Love" changed into fancier garb before stepping out for their film's world premiere in Rome, Italy on Friday (April 13).
Showing some love to Italian fans, the cast of "To Rome with Love" was spotted at a photocall in Rome today (April 13).
With her new movie "To Rome with Love" set to hit theaters later this month, Penelope Cruz added to the promotions by landing the cover of the May 2012 issue of Harper's Bazaar magazine.
Offering up a first look at the English/Italian movie, the trailer for "To Rome with Love" has been released by Yahoo Movies.


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Resilience Cuff $34
Sentiment Stone Locket $49
Legend Pendant $69
City Slim Clutch $59
Sutton Necklace $128
Engravable Disc Charm $39
Remy Wrap Bracelet $39
Pave Chevron Ring $29
Mercer Zip Wallet $118
Avalon Tote $148
Westwood Scarf $59
The Waverly Petite $99
We love the bold look of this neutral statement necklace. A gold Y-shaped silhouette with hints of mint enamel and cognac sparkle on a smooth gold plated chain.
Our promise to you....
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466 Washington Street, Attleboro, MA 02703
0 people saved this
BattlegroundZ is an indoor facility open year round offering black light, state-of-the-art laser tag, Paintball, Airsoft, Nerf-Style Wars, and full arcade. Reservations are not necessary, and we offer parties for all occasions and ages!
Of Note:
- Amenities: Accessible Facilities
HubWeek Festival Blends Art, Science & Technology
Massachusetts has an illustrious tradition of ideas, industry and innovation, plus an equally renowned creative...
Search All Listings Here.


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A modern yet timeless kind of education
If you're new to Waldorf education, at first it can seem so different. But as you learn just a bit more about it, it will start to feel very familiar. It's probably not unlike the school you went to when you were young; where the classroom was filled the smell of the chalkboard and the sound of sharpening pencils; where not everything was about preparing for the next test; where every child was an individual and learning could be fun.
Sanderling Waldorf School has been offering Waldorf education to north coastal San Diego families for almost 20 years. And while some might call it "old-fashioned", we prefer to think of it as timeless.
Learn more about Why Waldorf Works.
Upcoming events
See what else is on our school calendar.
Meet our faculty
The rich and diverse nature of Waldorf education attracts faculty with varied interests and from all walks of life. We're fortunate that our faculty and staff is no exception. (And they're all incredibly nice and good-looking too. Some people just have all the luck.)
A glimpse into Sanderling
Would you like to know more?
Well, we'd love to answer your questions! Give us a call or come by for a visit.


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Music: The Mechanisms
We were all once, every one of us — well, with the exception of the Toy Soldier, we were all once mortal and boring like your good selves. Until something within each of us broke. Shattered, beyond repair. And it was replaced by a fascinating individual by the name of Dr. Carmilla who, unfortunately, has since fallen out an airlock.The Mechanisms are a (currently) 9-piece band operating largely out of Oxford, UK. Offering retrospective futurist storytelling in the form of musical cabaret, they are a concept band consisting of immortal space pirates originally created by Dr. Carmilla as her backup band/companions. They've yet to shake their drive to perform, and have opted to embrace it by telling the tales of the things they've seen over the course of their long, long lives.The current performing roster is:
- Jonny d'Ville: Carmilla's first Mechanism (that he knows of) and also the crew's first mate. He and his mechanical heart don't offer much in the way of say, friendliness or leadership skills, but he is the chief storyteller.
- Ashes O'Reilly: Former mobster, enthusiastic arsonist and the crew's Quartermaster. Ashes and their mechanical lungs provide the band with bass guitar and occasional vocals.
- Drumbot Brian: Despite his designation as Drumbot, Brian is more frequently seen playing the banjo and the accordion. A scientist who was launched into space and left to die, his entire body save his heart was replaced by Carmilla. Once could describe him as the moral centre of the crew, but that would be foolish.
- The Toy Soldier: The Toy Soldier was never really mortal like the others, instead being a collectors item from a set of Toy Xs, but that didn't stop the Doc from fixing it up and installing it in the crew. Nobody really understands it or what it does, but it still happily provides mandolin, glockenspiel and vocals where required.
- Gunpowder Tim : The first Mechanism created by the crew in the absence of their Captain. He is a veteran of the war against the Moon Kaiser and is largely responsible for the destruction of the moon 3,000 years in the future ago. Assuming the role of gunner after the crew kindly replaced his eyes, he is well known for playing the guitar and singing some things. Though he is rumoured to be handy with a violin too.
- Marius von Raum: Ship's medic (not that they need one) and psychiatrist (not that they want one). He was found by the crew having already been mechanised by a mysterious stranger...
- Raphaella la Cognizi: Science officer who may or may not have cheated her way onto the ship after becoming a little too interested. Also she has wings. Brings gorgeous piano and vocals to the table.
- Anastasia Nikolaevna Romanova: better known as Nastya Rasputina; princess from the Empire of Cyberia. Ship's engenieer who largely favours machines over people, Nastya is most often seen playing the viola and violin.
- Ivy Alexandria: Ship's Archivist and Navigator whose positronic brain provides her with an impressive memory of facts and statistics at the expense of most of her memory of her life before joining the Aurora. She could be described as a one person woodwind section, having been spotted playing the recorder, oboe, flute, euphonium and the penny whistle at various shows.
Tropes featured by The Mechanisms as a whole:
- Audience Participation: The audience are invited to sing along with certain songs. See also Running Gag below.
- Awesome Mc Coolname: The whole crew.
- Ax-Crazy: Most of the crew at some point or another, especially Jonny if he gets bored. Also particularly true of Tim in his origin story, after his best friend is killed.
- Beard of Evil: Jonny d'Ville. Just look at him.
- Bittersweet Ending: See all their albums
- Concept Album: Concept Band, more like.
- Diesel Punk
- Detonation Moon: Tim's backstory
- Even Evil Has Standards: Jonny happily murders, robs and commits just about any crime you can imagine for fun, but never rape or any other sexual misdeed.
- Evil Feels Good: Regardless of the individual members' personal moralities, after so many years all of their ideas of "fun" vs "good" seems to have become a bit skewed.
- Heavy Meta
- "I Am Becoming" Song: All of the crew's origin songs to one degree or another.
- I Hate You, Vampire Dad: All of the Mechanisms who travelled with Carmilla seem to be pretty glad she's out of the picture (for now.) Jonny especially seems to have a lot of vitriol for her.
- Johnny McCoolname: Who do you think?
- Living Ship: The Aurora is a biomechanical vessel given sentience in the form of whatever the mechanising process is.
- The crew's engineer is also in a relationship with said ship.
- Murder Ballad: One-Eyed Jacks,
- Neoclassical Punk Zydeco Rockabilly: Why have one musical genre when you can have them all?
- Kill 'em All: Jonny killed his dad and everyone else. Tim blew up the moon. Ashes set their entire homeworld on fire.
- Just don't get attched to any characters in the story sets.
- Post Modernism
- Robosexual: Nastya, who is in a relationship with the Aurora.
- Robot or Spaceman Alter Ego
- Rule of Cool: Cyborg pirates created by their vampire captain on a biomechanical ship. In space.
- Running Gag: At the start of each live performance, Jonny introduces himself as the Captain. This is the cue for the audience (or, failing that, another Mechanism) to reply, "First Mate!"
- Space Pirates
- Spoken Word in Music: Par for the course when combining storytelling and song.
- Time Travel Tense Trouble: the war against the Moon Kaiser happened/will happen "three thousand years in the future ago".
- Thrown Out the Airlock: the fate of their creator Dr. Carmilla (allegedly - Jonny says it was an accident).
Tropes featured in their story sets:
Once Upon a Time (In Space)
- Black and Grey Morality: Snow admits that she and her rebel followers must be "brutal and cruel" in fighting the evil King Cole.
- Dark Lord on Life Support: Old King Cole
- Dude, She's Like, in a Coma!: Defied by Jonny in the Sleeping Beauty song:I'm not going to kiss a sleeping stranger, Nastya - that's really fucking creepy.
- (See Even Evil Has Standards, above.)
Ulysses Dies at Dawn
- A Good Way to Die
- And I Must Scream: After death, everyone on this world is trapped in deathless torture in the Acheron.
- Ax-Crazy: Heracles' 'service with a smile'
- Badass in a Nice Suit: The Suits, naturally
- Dead Partner: Orpheus
- Deal with the Devil: Several of the main characters make deals with Hades in Underworld Blues
- Driven to Suicide: Oedipus' mother/wife
- Drowning His Sorrows: Ulysses in Broken Horses
- Emerging from the Shadows: Daedalus
- Ensemble Cast
- Eye Scream: Oedipus
- Family Business: Ariadne
- Family Honor:
- Film Noir
- Goal in Life: "Ulysses simply seeks to rest" - their goal in life is to end their life
- I Die Free: Ulysses' final reward is to die somewhere the Ferrymen will never reach them, allowing them to escape the Acheron forever
- Professional Killer: Heracles.
- Shot to the Heart: Ariadne
- Slashed Throat: Orpheus
- Surprise Incest: Oedipus' wife
- The Crime Job: Heracles and Orpheus backed up Jason in The Fleece Job
- The Patriarch: Zeus
- The Reveal: Daedalus
- These Hands Have Killed: Heracles "With my bloodied hands, in service to the family"
- The Syndicate: The Olympians, anyone?
- Teeth-Clenched Teamwork: The Suits on occasions seem to be hellbent on pissing each other off, especially Heracles and...well, kind of everyone, but especially Orpheus.
High Noon Over Camelot
- All-Loving Hero: Mordred. That is, until he hits the Despair Event Horizon.
- Blood Knight: Gawain
- Cannibal Clan / Cannibal Tribe: The Saxon ghouls of Annwn, and Mordred's adopted family.
- Creepy Good: All of Galahad's songs are in a minor key and, although he has Camelot's best interests at heart, his fanaticism can be downright unnerving.
- Crowning Moment of Awesome: Galahad's last act.
- Sociopathic Hero: True of pretty much all the knights, with the exception of Mordred.
- The Power of Love: Arthur, Lancelot and Guinevere's love for each other prevents bloodshed when they discover only one of them can wield the GRAIL.
- Transsexual: Arthur's daughter, Morgause, grows up into a young man who takes the name Mordred.
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Midwest Industries Tactical Light Mount AR-15 Aluminum Matte
Product #: 968824 MI #: MCTAR-01G2 UPC #: 816537013013
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Aluminum tactical light mounts create firm anchor points for tactical lights.
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Material:6061 Aluminum
No gunsmithing required
Ambidextrous design
Fits any AR- series rifle, with a standard front sight.
Photo shows the side view, this mount has the same rail on the other side
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Material:6061 Aluminum
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Product is restricted by shipping carriers and cannot be shipped to certain locations or via certain shipping methods.
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CRN Channel News
In other top stories this week, Palo Alto Networks crushed its Q4. Also, a look at Apple's newest products.
GTDC Chief: PC, Tablet Sales Woes Made For Challenging 2015 Start For DistributorsU.S. PC and tablet sales fell off the map, and networking failed to replicate the success of late 2014, GTDC chair Tim Curran said at the GTDC Summit in San Francisco.
Dell To 'Respond Directly To Partners' In Uproar Over Microsoft Surface Pro Direct DealSolution providers with questions or concerns about Dell's decision to resell the Microsoft Surface Pro will soon get some answers straight from Dell, the company said.
Xerox Partners Are Upping Their Apps Game In Managed Print Services BlitzXerox partners are finding more recurring revenue opportunities with Xerox's new Innovate To Grow initiative.
10 Most Cash-Rich Solution Providers In Q2The 10 most cash-rich solution providers increased their holdings by 19.1 percent, to $14.38 billion, in the most recent quarter, with one channel partner stockpiling an additional $640 million to bankroll two acquisitions.
Boosting U.S. IT Skills Or Replacing U.S. Workers? H-1B Visas In The CrosshairsThe H-1B visa program has become mired in controversy, with proponents arguing it addresses tech worker shortages while naysayers claim it's used to replace American IT workers with foreigners. Here's how -- and why -- solution providers use the program.
10 Solution Providers With The Most Debt In 2015 Q2The 10 most debt-laden solution providers increased their debt load by more than 25 percent in the most recent quarter to $12.31 billion, with one foreign consulting giant making its way onto the list.
CloudLock Teams Up With CDW, PwCCloudLock CEO and founder Gil Zimmermann discusses the cybersecurity company's expanded channel program with CRNtv.
CRN's 2015 Annual Report Card WinnersTo celebrate the 30th anniversary of the Annual Report Card, CRN presented the winning vendors with their respective hardware in a private ceremony at XChange 2015.
2015's Annual Report Card Winners: A Grade AboveSolution providers have been grading their vendor partners in CRN's Annual Report Card for 30 years. Here is a detailed look at this year's scores.
Follow The Money: 12 Tech Venture Capital Investments In AugustVenture funding continues to flow to IT startups, especially in the areas of security and big data. Here's a look at 12 financing announcements that caught our attention.
5 Companies That Had A Rough WeekFor the week ending Sept. 4, CRN looks at IT companies that were unfortunate, unsuccessful or just didn't make good decisions.
Channel Beat: VMware CEO Tries To Contain Rumor MillIn other top stories from this week, Cisco and Apple team up. Plus, HP shops around its TippingPoint business before the company splits.
5 Companies That Came To Win This WeekFor the week ending Sept. 4, CRN takes a look at the companies that brought their 'A' game to the channel.
Channel Company Inks Deal With Zift To Strengthen SharedVue BusinessThe Channel Company is teaming with Zift Solutions in a move that aims to build a broader, deeper portfolio of channel marketing automation services to vendors that will drive channel revenue.
Maple Leaf Shocker: Compugen To Buy Metafore, Create $530M PowerhouseTwo of Canada's biggest solution providers are joining forces, with Compugen bolstering its cloud and managed services capabilities by purchasing 800-employee Metafore Technologies.
Sirius On The Prowl For Acquisitions As Kelso Preps To Buy Majority StakeIBM mainstay Sirius Computer Solutions plans to double down on mergers and acquisitions after a planned injection of capital from private equity giant Kelso & Co.
Lenovo Taps PC Group Veteran Tom Shell To Replace Former VP ParkerShell has been with Lenovo since 2006, most recently running the company's PC Business Group.
Managed Network Services Power SageNet Dives Into Security With Turnberry BuySageNet has bought the fast-growing cybersecurity practice of Turnberry Solutions to better protect its retail and energy clients.
30 Notable IT Executive Moves: August 2015The channel saw many of their favorite channel chiefs and executives jump ship to other vendors in August. Here are the top 30 IT executive moves of last month.


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- Is President Obama your ticket to paid maternity leave? — BabyCenter Blog
- Kourtney Kardashian and Penelope arrive in NYC in style — Celebrity Baby Scoop
- Lauren Holly gets real about raising tween boys — PEOPLE Moms & Babies
- Guess which season is best for raising athletes — The Bump
- How to remove crayon, glue, and other tough kid stains — Real Simple
- What it really feels like to hold a baby for the first time — HuffPost Parents
Latest Moms
My husband is a great dad but he can't do anything without my help. I'll ask him to get our son ready for bed while I clean and then I end up having to do everything. Sometimes I c ...


text: (Photo by Spencer Platt/Getty Images) [ Summer Gas Prices Could Jump if World Events Trigger Instability By John McKay April 2, 2014 Events in Russia (Ukraine) and the Middle East could cause spikes. Read More|Comment Category: Automotive, Tri-Cities News Tags: gas prices Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


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Column as I see 'em …
Let's start this week off by drilling a little more deeply into the library board's decision to spend $4 million on an 8,000 square foot expansion project, not to mention the funky, if not wholly improper, way the final decision was made.
First the good news. Those gnashing their teeth over the prospect of seeing a tax increase due to this expansion can chill. The library has about $2.6 million in reserve funds, which is more than the city council, fiscal court, school district and health department combined.
To the editor:
My apologies Mr. Carlson, if I have misinterpreted your statement (July 15th edition) regarding the black man's "perspective," but one needn't be black to be offended by slavery or by a symbol representing the defense of the right of a people to choose to legalize slavery.
I am not a history expert, but I do know that Kentucky was, of course, a border state in the Civil War, thus giving us ties with both heritages.
The family of the late Kenny Goodlett sincerely thanks all family and friends for their support, prayers, flowers, visits, cards, donations, food and phone calls after his recent passing.
During the days of his illness and weeks following his passing, we have been truly blessed with such an outpouring of love and support.
This past weekend, I had the pleasure of hosting a bridal shower for my sister. I asked her beforehand if she preferred a potluck style meal or a lighter meal, consisting of salads and finger foods.
She chose the latter, and boy did I have fun preparing the menu and the food. This week, I'd like to share with you what was served.
Chicken Salad
2 large chicken breasts, shredded
Mayonnaise to suit
1/4 to 1/2 tsp. salt
1/8 tsp. black pepper
Several dashes of cayenne pepper
1/2 tbsp. honey
As a parent you want your teen to make wise choices in relationships. You don't want them to get hurt and make life-changing mistakes.
Some mistakes are minor. Accept that teens will make mistakes in judgment. You probably did too when you were younger and no one is perfect even as an adult.
Anybody else feel like a duck? I had over 7 inches of rain in June, and July is shaping up to be just as wet. I've been here 19 years and this is definitely the wettest summer yet.
Grandma Nora would have called it "close." The high humidity makes you feel like you're wearing a wet towel around all day. On the plus side, I don't need as much moisturizer.
Green June beetle flight has begun across Kentucky.
They are similar to, and at the same time different from, Japanese beetles.
What they have in common
Both species are good fliers and congregate in large numbers when feeding. Also, each has one generation each year and their larval stages are white grubs that develop in soil.
Copyright © 2015
The Anderson News is your source for local news, sports, events, and information in Lawrenceburg, KY and the surrounding area.


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This IDC Retail Insights Perspective analyzes HCL Technologies, the global IT services arm of the US$6 billion HCL Enterprise and a leading provider of business transformation, enterprise and custom applications, infrastructure management, business process outsourcing (BPO), and engineering services.
Leveraging IDC Retail Insights experts' understanding of the competitive landscape and future outlook, this document highlights company and market information tailored to the needs of retail CIOs.
IDC Retail Insights: Asia/Pacific Retail IT Strategies , IDC Retail Insights: European Omni-Channel Retail IT Strategies
Tesco PLC, SAP AG, The Jones Group PLC, HCL, Target Australia Pty Ltd, IKEA Aktiebolag, Oracle Corporation, Microsoft Corporation, Pick n Pay Retailers Limited, JDA Software Group, Inc., Dixons Retail plc, IBM
Asia Pacific, Australia, Finland, Ireland, United Kingdom, United States, Western Europe
Analytic applications, Applications, Market intelligence, Marketing operations, Order management, Sales operations, Software, eCommerce
Consumer marketing and promotions, Consumer shopping, Fast moving consumer goods, Global retailing, Retail, Retail global supply chain, Retail investments, Store and online shopping experience


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Pauline Black at Festivals
Pauline Black (born 23 October 1953) is a British singer and actress, most notable as the lead singer of Ska / 2 Tone outfit The Selecter founded in 1979 in Coventry, UK. After the band split in 1982, Black developed an acting career in television and theatre, appearing in dramas such as The Vice, The Bill, Hearts and Minds and 2000 Acres of Sky. She won the 1991 Time Out award for Best Actress, for her portrayal of Billie Holiday in the play All or Nothing At All. She also starred next to Christopher Lee in the horror film, The Funny Man. Read more on Last.fm.
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- Willowman Festival 2011 - 19 Jun 2011 (Unspecified)
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Dr. Elizabeth Hay's Ratings
Friendly professional staff and Dr. Hay is great in the whole process of diagnosing and explaining your situation
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Dr. Hay is an amazing lady. She is highly respected by surgeons and colleagues in Canada! The complaints of waits in her off ice are silly as after having 8 eye surgeries, I at least recognize that eye appointments cannot happen immediately. Congratulations to Dr. Hay and her staff for all the work they do. Dr. Hay has a direct link to Drs. Mayberly and Mah in Vancouver and they too are simply amazing and perform many near miracle operations
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Unless you get in early, expect long waits. Hay's expertise is top notch, unfortunately she underestimates the intelligence of her patients. Often talks to her technicians as if the patient isn't in the room.
Was this rating useful? 0 [[ userState['ratings'][2831079].votes_count ]]
Dr. Hay is very rude and has very poor educate for a doctor. We need more doctors to have alternate places to go to.
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High strung and rude. Definitely no bedside manner. Would never return.
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I have seen her for 12 years and have only praise for this woman and her staff. When I began this eye journey there were two choices - Vancouver or Victoria. Having a local office with up-to-date technology and competent professionals is a godsend. For those who complain about the wait perhaps they should try the previous locations I have mentioned. Six hour wait in the Eye Center at VGH. How much of your time is your eyesight worth She has an organized, medically sound, multi-level assessment and treatment process which just takes time. Nevertheless when I have had an urgent problem I was seen and assessed within three hours of my call.
Was this rating useful? 1 [[ userState['ratings'][2682953].votes_count ]]
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Very slow disorganized office. Rude, ignorant and lazy staff. Did I say slow?
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did not catch glaucoma in donnas eye . when called and informed about sever pain in her eye an crippling headaches, we were told to go to are doctor and have her book a appointment with her. Even with are doctor requesting an emergency visit she was going to make us wait a week and a half for something she should have picked up on donnas visit that was only a month before.( we were told by a specialise that this should of been caught a yr. ago)So Donna when through pain and agony all thanks to dr.hays not doing her job. this also caused her to lose about 60% off her sight in her right eye. And not once did she call to see if donna was ok only her staff to make up false info re ; her appointments. Personally I would not trust this dr. because eyes do change they do not stay the same over a period of a year.
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I found Dr. Hay very knowledgeable, friendly and concerned about my eyesight. Staff are great and always helpful. The long wait people are complaining about is for the work needed (drops, testing, etc.) which needs to be done before you see Dr. Hay. I would not hesitate to recommend Dr. Hay.
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Archive for the 'doing the right thing' Category
"Whoops." Paper cites retracted gay canvassing paper — but blame me, says journal editor
By now, most Retraction Watch readers are likely familiar with the retraction in May of a much-ballyhooed study in Science on whether gay canvassers could persuade people to agree with same-sex marriage. It turns out that before that retraction appeared, a different study that cited the Science paper made its way online.
Kenneth Zucker, the editor of Archives of Sexual Behavior, which published the study online in February, 2015, decided he had some 'splaining to do. The article has now been published as the lead paper in the current issue of the journal, which also includes a comment from Zucker. He explains what happened: Read the rest of this entry »
Analysis of pilots with prostate cancer retracted for "inappropriate data"
In case any pilots out there are worrying about their risk of prostate cancer based on a recent meta-analysis that found they are at least twice as likely to develop the disease, they should relax — the paper has been retracted.
The reason: "including inappropriate data from two studies that should be ineligible."
"The risk of prostate cancer in pilots: a meta-analysis" reviewed eight studies to determine whether airline pilots, who are regularly exposed to radiation and other occupational hazards, have a higher incidence of prostate cancer. However, it also included studies that reported on prostate cancer among all U.S. Armed Forces servicemen, not pilots.
The retraction notice was posted in May — only months after it was published in Aerospace Medicine and Human Performance in February. The notice included a letter to the editor outlining flaws in the meta-analysis and an apologetic response from first author, David Raslau at the Mayo Clinic.
Here's the notice (appearing at the bottom of page 2):
What do you do after painful retractions? Q&A with Pamela Ronald and Benjamin Schwessinger
2013 was a rough year for biologist Pamela Ronald. After discovering the protein that appears to trigger rice's immune system to fend off a common bacterial disease – suggesting a new way to engineer disease-resistant crops – she and her team had to retract two papers in 2013 after they were unable to replicate their findings. The culprits: a mislabeled bacterial strain and a highly variable assay. However, the care and transparency she exhibited earned her a "doing the right thing" nod from us at the time.
After many months spent understanding what went wrong and redoing the experiments correctly, today Ronald and her team release another paper in Science Advances that reveals the protein they thought they had identified in 2013.
Ronald and co-first author Benjamin Schwessinger (who recently became an independent research fellow at the Australian National University in Canberra) spoke to us about the experience of recovering from the retractions and finally getting it right. The conversation has been edited for brevity and clarity.
-What did you do differently this time so you didn't repeat the same mistakes?
"To our horror": Widely reported study suggesting divorce is more likely when wives fall ill gets axed
A widely reported finding that the risk of divorce increases when wives fall ill — but not when men do — is invalid, thanks to a short string of mistaken coding that negates the original conclusions, published in the March issue of the Journal of Health and Social Behavior.
The paper, "In Sickness and in Health? Physical Illness as a Risk Factor for Marital Dissolution in Later Life," garnered coverage in many news outlets, including The Washington Post, New York magazine's The Science of Us blog, The Huffington Post, and the UK's Daily Mail .
But an error in a single line of the coding that analyzed the data means the conclusions in the paper — and all the news stories about those conclusions — are "more nuanced," according to first author Amelia Karraker, an assistant professor at Iowa State University.
Karraker — who seems to be handling the case quickly and responsibly — emailed us how she realized the error:
Misidentified genetic sequence causes retraction of pathogen paper one month after publication
The author of an article mapping the genome of an infectious bacterium is pulling the paper because — well, it wasn't the bacterium she thought it was.
Study author Celia Abolnik is retracting her paper in Genome Announcements because it didn't actually map out the DNA of Mycoplasma meleagridis, a bacterium that typically infects turkeys but has recently been found in chickens.
The trouble was, the sequence for Mycoplasma meleagridis in the National Institute of Health's DNA database, Genbank, was actually a different variety of bacteria — Mycoplasma gallinaceum, another scourge of poultry.
Here's the notice for "Complete Genome Sequence of Mycoplasma meleagridis, a Possible Emerging Pathogen in Chickens:"
Rabbit redo: Paper on lepus hepatitis pulled for mutation that "was not supposed to be present"
The authors of recent article about the rabbit hepatitis E virus have pulled the paper after discovering an unexpected mutation in their viral clone that likely affected the analysis.
They realized their mistake soon after the article, "RNA transcripts of full-length cDNA clones of rabbit hepatitis E virus are infectious in rabbits," was published online in the Journal of General Virology in November, 2014. They withdrew the article before it made it into print.
The article came from a group led by Xiang-Jin Meng, of the Virginia-Maryland College of Veterinary Medicine, an offshoot of Virginia Tech and the University of Maryland.
Here's the notice, which — tsk tsk — sits behind a pay wall: Read the rest of this entry »
The consequences of retraction: Do scientists forgive and forget?
Here at Retraction Watch, we are reminded every day that everybody (including us) makes mistakes — what matters is, how you handle yourself when it happens. That's why we created a "doing the right thing" category, to flag incidents where scientists have owned up to their errors and taken steps to correct them.
We're not suggesting retractions have no effect on a scientist's career — a working paper posted last month by the National Bureau of Economic Research found that principal investigators with retracted papers see an average drop of 10% in citations of their other papers, a phenomenon known as a citation penalty. But they face a bigger penalty if the retraction stemmed from misconduct, rather than an honest mistake.
This jibes with research we've seen before, which shows the scientific community can be forgiving when researchers own up to their mistakes – notably, a 2013 study that found scientists face no citation penalty if they ask to retract their own papers, rather than forcing the journal or publisher to act.
Fungus among us, but what kind? Typing error spawns retraction for mushroom paper
As every mushroom lover knows, weekend mycology is no sport for the lily-livered. Tasty species often look awfully like their deadly cousins. Turns out, typing can even be problematic for the experts.
Natural Products Research is retracting a 2014 paper on shelf fungus because… well, it wasn't about shelf fungus after all.
The paper, "Chemical constituents: water-soluble vitamins, free amino acids and sugar profile from Ganoderma adspersum," was written by Ibrahim Kivrak, a food chemist at Mugla Sitki Kocman University in Mugla, Turkey. It analyzed the nutritional components of G. adspersum, and found, per the abstract:
"[T]hese things can happen in every lab:" Mutant plant paper uprooted after authors correct their own findings
Three biologists at Tokyo Gakugei University in Japan have retracted a 2014 Frontiers in Plant Science paper on abnormal root growth in Arabidopsis "in light of new experimental evidence" showing they fingered the wrong mutant gene. The journal editors are hailing the retraction as an "excellent example of self-correction of the scientific record."
The paper, "Mechanosensitive channel candidate MCA2 is involved in touch-induced root responses in Arabidopsis," described the abnormally behaving roots of a mca2-null mutant Arabidopsis plant.
A subsequent string of experiments by the same research team—including DNA microarrays, RT-PCR, and a PCR-based genomic deletion analysis—demonstrated that two other mutations that somehow creeped into their experimental populations may have been to blame for the abnormal root behavior.
It's a notably thorough and informative retraction notice from Frontiers, an open-access publisher with a history of badly handled and controversial retractions and publishing decisions. The notice describes the new experiments and the previous, erroneous results: Read the rest of this entry »
Chip slip: Irreproducibility erases computer memory paper
Researchers at the Chinese Academy of Sciences have retracted a paper in Nanoscale about an experimental computer chip after they were unable to recreate their published results.
"We retract this article to avoid misleading readers and intend to undertake further tests to confirm our previous results," they write in the notice.
The scientists are working on developing a chip that uses resistive random-access memory, which allows a huge amount of information to be stored in a tiny package and accessed quickly while using very little power. A number of companies are working on the technology, but none have successfully commercialized it.
Here's the notice for "High uniformity and improved nonlinearity by embedding nanocrystals in selector-less resistive random access memory" (free, but requires login): Read the rest of this entry »


text: Friday night was a long one for my children. Two of their friends came for a sleepover, and with all four children snuggled into the big sofa bed together, there wasn't a lot of sleep happening. In anticipation of her buddy coming over, my five-year old daughter announced that they would stay up until midnight. So when the kids weren't looking, I changed the digital clocks on the microwave and the stove (which they could see from the living room) so that midnight would happen a couple of hours sooner.


text:
Page 1
Formation and Function of the Myofibroblast during
Tissue Repair
Boris Hinz1
It is generally accepted that fibroblast-to-myofibroblast differentiation represents a key event during wound
healing and tissue repair. The high contractile force generated by myofibroblasts is beneficial for physiological
tissue remodeling but detrimental for tissue function when it becomes excessive such as in hypertrophic scars,
in virtually all fibrotic diseases and during stroma reaction to tumors. Specific molecular features as well as
factors that control myofibroblast differentiation are potential targets to counteract its development, function,
and survival. Such targets include a-smooth muscle actin and more recently discovered markers of the
myofibroblast cytoskeleton, membrane surface proteins, and the extracellular matrix. Moreover, intervening
with myofibroblast stress perception and transmission offers novel strategies to reduce tissue contracture;
stress release leads to the instant loss of contraction and promotes apoptosis.
Journal of Investigative Dermatology (2007) 127, 526–537. doi:10.1038/sj.jid.5700613
It is generally accepted that myofibro-
blasts represent key players in the
physiological reconstruction of con-
nective tissue after injury and in gen-
eratingthe pathological
deformations that characterize fibrosis
(Gabbiani, 2003; Desmouliere et al.,
2005). In previous reviews, we have
focused on the role of cell–cell and
cell–matrix contacts in myofibroblast
development and function (Hinz and
Gabbiani, 2003a,b; Hinz, 2006). Here,
I draw a more general picture how the
mechanical and chemical microenvir-
onments integrate to promote tissue
remodeling by myofibroblast. Differen-
tiation of fibroblasts into myofibroblasts
can be understood as a two-step
process: (1) to re-populate damaged
tissues, fibroblasts acquire a migratory
phenotype by de novo developing
contractile bundles. These in vivo stress
fibers are first composed of cytoplasmic
actins and generate comparably small
traction forces (Hinz et al., 2001b). We
have recently proposed the term ''pro-
to-myofibroblast'' to discriminate such
activated fibroblasts from quiescent
fibroblasts that are devoid of any
contractile apparatus in most intact
tissues (Tomasek et al., 2002). This first
phenotypic change occurs in response
to changes in the composition, organi-
zation, and mechanical property of the
extracellular matrix (ECM) (Hinz and
Gabbiani, 2003b) and to cytokines
locally released by inflammatory and
resident cells (Werner and Grose,
2003). (2) With increasing stress in the
ECM resulting from their own remodel-
further develop into ''differentiated
myofibroblasts'' by neo-expressing a-
smooth muscle actin (a-SMA), the most
widely used myofibroblast marker. Ex-
pression of a-SMA is precisely con-
trolled by the joint action of growth
factors like transforming growth factor
(TGFb1), of specialized ECM proteins
like the fibronectin (FN) splice variant
ED-A FN, and of the mechanical
2002). Incorporation of a-SMA into
stress fibers significantly augments the
contractile activity of fibroblastic cells
(Tomasek etal.,
and hallmarks the contraction phase of
connective tissue remodeling (Hinz
et al., 2001a).
It has to be noted that the contribu-
tion of myofibroblast contraction to
physiological tissue remodeling has
been questioned by a study reporting
normal closure of pig full thickness
wounds despite repeated excision of
the central and peripheral granulation
tissue (Gross et al., 1995). However, rat
wounds that were kept open for 10
days with a plastic frame and have then
been released from the splint contract
to B50% of their initial size within
6hours; this cannot be explained by
enhanced proliferation of fibroblasts
and keratinocytes at the wound edge.
Hence, the porcine skin may be able to
compensate for the experimentally in-
duced chronic loss of granulation tissue
by mechanisms that have not yet been
elucidated. Such a compensatory me-
chanism appears to function in a-SMA-
knockout mice that macroscopically
exhibit almost normal wound closure
(personal communication, J.J. Toma-
sek, University of Oklahoma Health
526Journal of Investigative Dermatology (2007), Volume 127
& 2007 The Society for Investigative Dermatology
Received 29 May 2006; revised 6 July 2006; accepted 17 July 2006
1Laboratory of Cell Biophysics, E´cole Polytechnique Fe ´de ´rale de Lausanne (EPFL), Lausanne, Switzerland
Correspondence: Dr Boris Hinz, Laboratory of Cell Biophysics, E´cole Polytechnique Fe ´de ´rale de Lausanne (EPFL), Ba ˆtiment SG –AA-B 143, Station 15, CH-1015
Lausanne, Switzerland. E-mail: email@example.com
Abbreviations: a-SMA, a-smooth muscle actin; ECM, extracellular matrix; FA, focal adhesion; Fizz, found in inflammatory zone; FN, fibronectin; LAP, latency-
associated protein; LTBP-1, latent TGFb1-binding protein; SMC, smooth muscle cell; TGF, transforming growth factor
Page 2
Sciences Center, Oklahoma City, OK).
These mice appear to substitute for a-
SMA by de novo expressing other
muscle actin isoforms like g-smooth
muscle and a-skeletal actin, which also
explains why blood pressure is surpris-
ingly little affected by the lack of a-
SMA in vascular smooth muscle cells
(SMCs) (Schildmeyer et al., 2000). In
contrast to these chronic conditions,
acute inhibition
contraction by intracellular delivery of
the specific N-terminal
AcEEED of a-SMA significantly reduces
wound contraction (Hinz et al., 2002).
It will be interesting to test whether
or mice treated with a-SMA RNAi
will exhibit similarly impaired wound
In physiological remodeling such as
during dermal wound healing, the
contractile activity of myofibroblasts is
terminated when the tissue is repaired;
a-SMA expression then decreases and
myofibroblasts disappear by apoptosis
(Desmouliere et al., 1995). In patholo-
gical wound healing, however, myofi-
broblast activity persists and leads to
tissue deformation, which is particu-
larly evident in hypertrophic scars
developing after burn injury, in the
fibrotic phase of scleroderma and in the
palmar fibromatosis of Dupuytren's
disease (Schurch et al., 2006). Myofi-
also characteristic for fibrosis affecting
vital organs such as the liver (Desmou-
liere et al., 2003), heart (Virag and
Murry, 2003; Brown et al., 2005), lung
(Phan, 2002; Thannickal et al., 2004),
and kidney (Lan, 2003). In addition,
myofibroblast participation
process called stroma reaction pro-
motes cancer progression by creating
a stimulating microenvironment for
epithelial tumor cells (De Wever and
Mareel, 2003; Desmouliere et al.,
2004). It becomes increasingly ac-
cepted that stroma cells represent im-
portant targets of anticancer treatments
(Bissell and Radisky, 2001; Liotta and
Kohn, 2001; Mueller and Fusenig,
2004). In the light of such severe
consequences of myofibroblast appear-
ance and dysfunction, the necessity of
more profoundly understanding the
molecular mechanisms of myofibro-
of myofibroblast
blast formation and function appears
Myofibroblast origin
The classical view on dermal wound
healing implies local recruitment of
fibroblasts from the dermis of the intact
adjacent skin to sites of inflammation
(Desmouliere et al., 2005). Pericytes
and SMC from the vasculature have
been proposed as another local myofi-
broblast source in scleroderma (Rajku-
mar et al., 2005) as well as liver and
glomerular fibrosis (Desmouliere et al.,
2003). In addition, fibroblasts may
originate from fibrocytes, a sub-popu-
lation of bone marrow-derived leuko-
cytes with fibroblast
(Abe et al., 2001). This concept has
recently been revisited by transplanting
bone marrow from (1) male to irra-
diated female mice and identifying the
Y chromosome by in situ hybridization
(Direkze et al., 2003) and (2) from
transgenic green fluorescent mice to
irradiated wild-type animals (Hashimo-
to et al., 2004). These studies reveal a
surprisingly high fraction of 30–50% of
the wound myofibroblasts potentially
deriving fromfibrocyte
(Direkze et al., 2003; Ishii et al.,
2005; Mori et al., 2005). Comparable
proportions have been demonstrated
for myofibroblasts appearing during
fibrosis of the liver (Forbes et al.,
2004), kidney (Direkze et al., 2003),
and lung (Hashimoto et al., 2004) and
during the stroma reaction to epithelial
tumors (Ishii et al., 2003). It remains to
be seen whether myofibroblasts from
different origins exhibit different char-
acteristics and functions during tissue
repair as suggested for liver fibrosis
(Guyot et al., 2006) or whether the
organism is recruiting myofibroblast
precursors from several sources to
satisfy the temporarily high demand of
contractile cells, which may all follow
a similar differentiation program.
Identification of the myofibroblast – a
The question of the myofibroblast
origin is closely related to the problem
of its identification. Three major ultra-
structural features discriminate myofi-
broblasts from quiescent fibroblasts in
tissues: (1) bundles of contractile mi-
crofilaments, (2) extensive cell-to-ma-
trix attachment
intercellular adherens and gap junc-
tions (Eyden, 2005; Schurch et al.,
2006). However, this definition has its
limits when myofibroblasts need to be
discriminated from other contractile
cell types like SMC, requiring specific
molecular markers.
sites,and (3)
Cytoskeletal markers of the myofibro-
blast. The most frequently employed
myofibroblast marker is a-SMA, which
evidently fails to distinguish between
myofibroblasts and SMC in situations
that exhibit mixed populations. For
example, remodeling of injured arteries
is thought to be predominantly driven
by SMC from the media but a contribu-
tion from adventitial fibroblasts has
also been suggested (Sartore et al.,
2001; Zalewski et al., 2002). Contrac-
tile SMC specifically express smooth
muscle myosin heavy chain, h-caldes-
mon, and desmin; however, SMC loose
these markers when acquiring a syn-
placed in culture (Christen et al.,
2001). Until recently, smoothelin was
suggested a late differentiation marker
for SMC that is not expressed in
myofibroblasts (van der Loop et al.,
1996). However, gene expression pro-
filing supported by protein biochemis-
try revealed induction of smoothelin
and other late SMC markers in TGFb1-
(Chambers et al., 2003). Very recently,
the 4Ig isoform of the stress fiber
protein palladin has been proposed as
novel marker for myofibroblast differ-
entiation (Ro ¨nty et al., 2006), but
Western blotting analysis with pan-
palladin antibodies indicates expres-
sion of this isoform also in SMC
(Mykkanen et al., 2001). Hence, at
present no cytoskeletal protein allows
to reliably discriminate between myo-
fibroblasts and SMC; however, recent
advances in proteomics and gene array
analysis may lead to the identification
of such a unique marker of the myofi-
broblast, provided that it exists (Cham-
bers et al., 2003; Malmstrom et al.,
and afterbeing
lung fibroblasts
The myofibroblast surface. Of particu-
lar interest not only for the purpose of
B Hinz
Myofibroblast Differentiation
Page 3
identification but also for the delivery
of specific drugs are proteins specifi-
cally expressed on the plasma mem-
membrane protein Thy-1 is frequently
used for the inverse approach as it is
expressed by fibroblasts but absent
from differentiated
(Koumas et al., 2003). Interestingly,
Thy-1-negative cells fail to respond to
fibrogenic stimuli suggesting that Thy-1
expression characterizes a specific sub-
population of fibroblasts that may not
be able to undergo myofibroblast dif-
ferentiation (Zhou et al., 2004; Hagood
et al., 2005). A promising new strategy
to target and identify myofibroblasts is
the expression of specific cadherins
(Hinz and Gabbiani, 2003a), trans-
membrane cell–cell adhesion proteins
that are intracellularly linked to the
actin cytoskeleton (Gumbiner, 2005).
In contrast to virtually cadherin-nega-
tive fibroblasts of normal dermis, proto-
myofibroblasts of
tissue and in culture express N-cadher-
in (cadherin-2, A-cell adhesion mole-
cule (A-CAM)) (Hinz et al., 2004). In
conjunction with the appearance of a-
SMA after TGFb1-treatment in culture
or in differentiated myofibroblasts of
contractile wound granulation tissue,
placed by OB-cadherin (cadherin-11).
OB- but not N-cadherin seems to play a
functional role in coordinating myofi-
broblast contraction in populations
(Hinz et al., 2004). A similar shift from
N- to OB-cadherin expression has been
described in stroma fibroblasts reacting
against human prostate cancer progres-
sion (Tomita et al., 2000). OB-cadherin
is absent from SMC but it is expressed
on a variety of cell types of mesench-
ymal origin; hence, it cannot be con-
sidered as unique myofibroblast surface
gradually re-
The ECM of myofibroblast-populated
tissue. In addition to producing tension
for remodeling, enhanced ECM synthe-
sizing and processing activity signifi-
cantly contributes to tissue remodeling.
Myofibroblasts produce several com-
ponents of the ECM that can potentially
be used as molecular markers, depend-
ing on the context of myofibroblast
appearance; the most prominent myo-
fibroblast ECM products are collagens
of types I, III, IV, and V (Schurch et al.,
2006) which, however, are produced
by a variety of cells. More recently,
collagen type VI attracted attention as it
is upregulated together with myofibro-
blast differentiation in human renal
fibrosis (Groma, 1998), in myocardial
interstitial fibrosis (Kitamura et al.,
2001), and in the stroma of hepatocel-
lular carcinoma (Faouzi et al., 1999).
Interestingly, culturing cardiac fibro-
blasts on collagen type VI substrates
induces myofibroblast differentiation
but not culture on collagen types I
and III (Naugle et al., 2006). At present,
the most reliable marker of the myofi-
broblast ECM is the FN splice variant
ED-A FN (Serini et al., 1998). ED-A FN
is also expressed in low amounts by
fibroblastic cells in culture (Dugina
et al., 2001; Hinz et al., 2001a) and
by vascular SMC in vivo and in vitro
(Glukhova et al., 1989). Another com-
ponent of the myofibroblast ECM,
glycoprotein tenascin-C is associated
with tissue repair phenomena (Chiquet-
Ehrismann and Chiquet, 2003). Tenas-
cin-C appears to attract fibroblasts and
to promote their differentiation into
myofibroblast in injured tissue (Tamao-
ki et al., 2005) and at the tumor
invasion front of cancers (De Wever
et al., 2004). However, the shared
expression in SMC limits its usage as
myofibroblast marker (Chiquet-Ehris-
mann and Chiquet, 2003).
In view of the expression profile of
cytoskeletal and ECM proteins, the
differentiated myofibroblast appears to
be situated in a continuous spectrum
existing between fibroblasts and SMC.
It may be necessary to combine com-
mon markers of the contractile cell
phenotype with the exclusive surface
expression of proteins like OB-cadherin
and Thy-1 to unmistakably discriminate
and SMC.
Chemical factors inducing myofibroblast
Apart from being important diagnostic
tools, myofibroblast-specific proteins
are likewise potential targets to mod-
ulate myofibroblast differentiation and/
or contractile function; this has been
shown by interfering with a-SMA (Hinz
et al., 2002) and with ED-A FN (Serini
et al., 1998). Alternative antifibrosis
strategies aim to prevent development
physiological cytokines that control
myofibroblast differentiation. TGFb1 is
considered the major growth factor
directly promoting myofibroblast de-
velopment by inducing expression of a-
SMA (Desmouliere et al., 1993; Ron-
nov-Jessen and Petersen, 1993), ECM
proteins (Werner and Grose, 2003),
and a number of cytoskeletal proteins
that construct the myofibroblast con-
tractile apparatus (Malmstrom et al.,
2004). TGFb1 effects are ''fine-tuned''
by cooperative or antagonistic growth
factors and some recent studies report
myofibroblast differentiation
absence of TGFb1 signaling.
by affecting
in the
Control of a-SMA transcription by
TGFb1 signaling. The major pathway
through which TGFb1 regulates expres-
sion of a-SMA in fibroblastic cells
appears to involve Smad signaling
(Figure 1). Binding of active TGFb1 to
the TGFb receptor type II leads to the
phosphorylation and recruitment of
TGFb receptor type I into a heteromeric
receptor complex. The serine/threonine
kinase activity of the activated complex
phosphorylates Smad2 and Smad3, that
each bind to Smad4 and translocate
into the nucleus to enhance gene
transcription by
DNA transcription factors (Feng and
Derynck, 2005; Massague et al., 2005).
Transcription of a-SMA in lung myofi-
broblastsand in
activated hepatic stellate cells is pre-
dominantly mediated by the binding of
Smad3 to the Smad-binding element 1
upstream of the a-SMA core promoter
sequence; the role of Smad3 binding to
a secondSmad-binding
(Smad-binding element 2) in the core
region is unclear at present (Hu et al.,
2003; Uemura et al., 2005). In contrast,
another study demonstrated that over-
expression of Smad2 but not of Smad3
induces myofibroblast differentiation in
lung fibroblasts (Evans et al., 2003); this
discrepancy may be due to different
roles of Smad2 and Smad3 depending
on the level of myofibroblast differen-
tiation (Liu et al., 2003). Moreover,
rather than being essential factors for a-
cooperating with
528Journal of Investigative Dermatology (2007), Volume 127
B Hinz
Myofibroblast Differentiation
Page 4
SMA transcription, Smad 2/3 should be
considered as modulators of the activ-
ity of other transcription factors. This
may explain different results obtained
from acute removal of Smad, for
example, by using an antisense ap-
proach compared with chronic Smad
deficiency in knockout animals. In the
first setting, cells may not be able to
compensate for the instant loss of the
important modulating
Smads; adaptation and compensation
may, however, occur in the knockout
Alternatively, TGFb1 can regulate
fibroblast gene expression indepen-
dently from Smad signaling (Derynck
and Zhang,2003;
Heldin, 2005) and expression of a-
SMA has been documented during the
activation of Smad3-null hepatic stel-
late cells in culture (Schnabl et al.,
2001). One pathway of Smad-indepen-
dent TGFb1 induction of the myofibro-
blastic phenotype has been revealed in
fected with dominant-negative Smad2
and appears to function via activating
phosphatidylinositol 3-kinase and the
downstream effector p21-activated ki-
nase-2; expression of a-SMA has not
been assessed in this study (Wilkes
et al., 2005). Smad-independent tran-
scription of a-SMA in fibroblasts is
regulated via the TGFb1 control ele-
ment (Roy et al., 2001; Tomasek et al.,
2005) that together with the TGFb1
binding site for the transcriptional
activator proteins Sp1/2, members of
(Cogan et al., 2002; Subramanian
etal.,2004). Another
element for a-SMA transcription in
myofibroblasts and SMC is the MCAT-1
site that is enhanced by binding of
MCAT-suppressor proteins; the pre-
sence of a second MCAT element
further upstream of the promoter ap-
pears not crucial (Swartz et al., 1998;
Carlini et al., 2002).
Importantly, transcription of a-SMA
in SMC differs from fibroblasts by being
additionally regulated via serum-re-
sponse factor binding to CC(A/T)6GG-
like sequence motifs (CArG elements)
in the promoter region (Hautmann
et al., 1997); these elements seem not
familyof kru ¨ppel-likefactors
TGF? receptor
type ll
TGF? receptor
type l
Control function for ?-SMA transcription in fibroblasts:
Mandatory Not crucial
?-SMA core promoter
Figure 1. Regulation of a-SMA transcription in myofibroblasts. The major pathway of TGFb1-induced a-SMA expression in myofibroblasts is mediated via
Smad3 activation by the TGFb1 receptor complex, leading to Smad3 association with Smad4 and translocation into the nucleus. Smad3 binding to Smad-
binding elements in the promoter region regulates a-SMA transcription in conjunction with a variety of transcription factors (TF). Some TGFb1-antagonizing
factors like IFN-g operate via activation of YB-1 that inhibits Smad3-enhanced gene transcription and upregulates expression of the inhibitory Smad7. TGFb1-
induced, Smad-independent transcription of a-SMA is enhanced by binding of the kru ¨ppel-like factors Sp1/3 to the TGFb1 control element and the TGFb1
hypersensitivity region. Moreover, binding of the TEF-1 to the MCAT-1 element is crucial for a-SMA expression in myofibroblasts and SMCs. In contrast to SMC,
interaction of the serum-response factor with CArG elements A, B, C, and D is not mandatory for a-SMA transcription; however, the intronic CArG element
regulates a-SMA transcription in both cell types. Please refer to text for details and references.
B Hinz
Myofibroblast Differentiation
Page 5
to be required for a-SMA transcription
in myofibroblasts (Roy et al., 2001). In
contrast, the CArG element in the first
intron promoter region has recently
been demonstrated to regulate a-SMA
transcription in myofibroblasts similar
to SMC (Tomasek et al., 2005). It
remains to be shown whether upregu-
lated serum-response factor in response
to mechanical stimulation (Wang et al.,
2006) acts predominantly through this
intronic CArG element to enhance a-
SMA expression. Deciphering the dis-
tinct upstream events in each cell type
may provide future gene targeting
strategies to specifically inhibit myofi-
broblast formation without affecting
SMC function.
TGFb1 in myofibroblast differentia-
tion. One of the best studied cytokines
induced by TGFb1 is connective tissue
growth factor that potentiates the profi-
brotic action of TGFb1 and at the same
time induces fibroblast proliferation
(Leask et al., 2002). These pleiotrophic
effects have been attributed to distinct
connective tissue growth factor subdo-
mains and to the mutually exclusive
cooperation with other cytokines like
EGF and IGF-2 (Grotendorst and Dun-
can, 2005). Connective tissue growth
factor cooperates with TGFb1 but does
not substitute for its action, as a-SMA
expression remains unchanged after
administration of recombinant connec-
tive tissue growth factor to cultures of
corneal fibroblasts (Folger et al., 2001).
A novel cooperative factor of TGFb1
seems to be the cell-surface protein
galectin-3. Galectin-3 is mandatory for
TGFb1-induced myofibroblast differen-
tiation of hepatic stellate cells in
culture and is upregulated in experi-
mental liver, kidney, and lung fibrosis
(Henderson et al., 2006). Knockout of
galectin-3 significantly reduces hepatic
fibrosis at unchanged levels of TGFb1
and inhibits myofibroblast activation of
cultured stellate cells in the presence of
TGFb1; addition of recombinant galec-
tin-3 rescues myofibroblast differentia-
tion. Binding of galectin-3 to growth
factor receptors has been demonstrated
but its cooperation with TGFb1 is not
yetunderstood (Henderson
factors cooperatingwith
et al.,
TGFb1-induced myofibroblast differ-
entiation. Attractive with respect to
therapeutic treatment of fibrosis are
growth factors that antagonize TGFb1
and thereby reduce myofibroblast dif-
ferentiation. The inflammatory media-
tor IL-1 efficiently inhibits TGFb1-
induced a-SMA expression in cultured
dermal fibroblasts when added as
recombinant protein (Shephard et al.,
2004b); overexpression of the intracel-
lular IL-1 receptor antagonist (IL-1ra)
has similar effects (Kanangat et al.,
2006). Co-culture experiments with
fibroblasts suggest that time-controlled
secretion of IL-1 by keratinocytes may
be one mechanism during cutaneous
wound healing to suppressing fibro-
early wounds(Shephard
2004b). IFN-g, a cytokine produced
by T cells also reduces a-SMA expres-
sion in cultured fibroblasts. This effect
appears to be mediated by activation of
the repressor protein YB-1, which
translocates to the nucleus and inter-
feres with Smad3-mediated transcrip-
tion of TGFb1-induced genes (Higashi
et al., 2003) (Figure 1). In addition, YB-
1 enhances the transcription of Smad-7,
a negative regulator of Smad3 signaling
(Dooley et al., 2006).
factorsthat antagonize
transition in
Myofibroblast differentiation without
TGFb1?. Only few factors have been
identified that potentially induce myo-
fibroblast differentiation independently
from TGFb1. IL-6 has been suggested to
be such a factor as IL-6-null mice
differentiation at unchanged levels of
TGFb1. Moreover, recombinant IL-6
increases a-SMA transcription in fibro-
blast cultures from IL-6-null mice in the
absence of exogenous TGFb1 (Gallucci
et al., 2006). Similarly, nerve growth
factor enhances a-SMA expression in
cultured skin and lung fibroblasts (Mi-
cera et al., 2001). However, as myofi-
broblast differentiation in response to
IL-6 and nerve growth factor was not
tested with simultaneous inhibition of
TGFb1 signaling,
autocrine TGFb1 cannot be ruled out.
Very recently, Fizz1 (found in inflam-
matory zone), a novel protein secreted
by alveolar epithelial cells, has been
demonstrated to undergo dramatic up-
regulation in an animal model of lung
fibrosis. When added to cultured fibro-
blasts, recombinant Fizz1 induces ex-
pression of a-SMA in the absence of
TGFb1; the molecular mechanism of
Fizz1 action remains elusive (Liu et al.,
2004). In addition to proinflammatory
cytokines, agonists of myofibroblast
contraction, like angiotensin-II (Swa-
ney et al., 2005), endothelin-1 (Shi-
Wen et al., 2004), and thrombin
(Bogatkevich et al., 2003) induce ex-
pression of a-SMA expression in vitro;
however, it is unclear whether endo-
genousTGFb1 contributes
effect. It is also conceivable that con-
traction agonists enhance a-SMA ex-
pression by augmenting the level of
intracellular stress (Shephard et al.,
to this
Myofibroblasts are controlled by the
mechanical microenvironment
Despite high levels of active TGFb1 in
early wounds (Yang et al., 1999),
expression of a-SMA and enhanced
myofibroblast contraction are restricted
to the later phases of dermal wound
healing. Earlier myofibroblast appear-
ance may be suppressed by antagonis-
tic factors released by inflammatory
cells and keratinocytes. Moreover, it
becomes increasingly clear that myofi-
broblast development is profoundly
influenced by the mechanical micro-
environment, in particular, by the
organization and stiffness of the ECM
(Hinz and Gabbiani, 2003a). The level
of a-SMA expression in cultured differ-
entiated myofibroblasts increases with
increasing matrix rigidity as demon-
strated using collagen and polyacryla-
mide gel substrates of varying stiffness
(Arora et al., 1999; Hinz et al., 2003).
Mechanically preventing wound clo-
sure by splinting the edges of experi-
mental wounds accelerates expression
of a-SMA compared with normally
healing wounds; stress release by re-
moving the splint leads to reduced a-
SMA expression (Hinz et al., 2001b).
TGFb1 is always present in these
conditions; however, the mechanical
characteristics of the environment ap-
pear to modulate its action to induce
either migration or contraction (Grin-
530 Journal of Investigative Dermatology (2007), Volume 127
B Hinz
Myofibroblast Differentiation


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Kendra and Raymond | Sneak Peak | English Inn
Had the pleasure of photographing this beautiful wedding and reception at the always lovely English Inn of EatonView full post »
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Aryn and Dean were wed on a beautiful May day at one of my all time favorite wedding locations, Millcreek Barn inView full post »
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It wasn't hard to love this wedding, gorgeous day, adorable and sweet couple, and The Blue Dress Barn in BentonView full post »
Sarah and Jeffery | 04.25.15 | English Inn
A sweet intimate ceremony and dinner at the English Inn. If you are having a small wedding or even eloping please getView full post »
Chelsea and James | 04.18.15 | MSU Alumni Chapel Wedding
Chelsea and James were wed on the perfect spring day. Flowers blooming and tiny leaves on the trees, I love spring! TheView full post »
Gloria and Scott | Engaged | Engagement photos at The English Inn
When Gloria first got in touch with me to inquire about my services her first sentence was…"My name isView full post »
Hannah and Mark | 02.07.15 | English Inn Wedding Eaton Rapids
Hannah and Mark were wed on a sunny February day. It was a balmy 40 degrees which was more than a little welcome afterView full post »
Ashley and Adam | Engaged | Ada Winter Engagement Photography
Had such a lovely time photographing this beautiful couple on a chilly but gorgeous January day. We started at theirView full post »


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Norman Rockwell's World of ScoutingOriginal Price:$24.95 Current Price: $12.98In this comprehensive collection, Joseph Csatari tells the story behind the more than 50 paintings Norman Rockwell created for the Scouts. He shares his experiences of mentoring with Rockwell and then assuming the official-artist position himself. Csatari's 40+ Scouting paintings are featured as well. Licensed hardback publication, a must-have for all Scouting libraries. Learn More
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Magnetic-Go Chess$9.99Weighing in at less than a pound, this is the perfect magnetic travel game to keep your Scouts entertained on the trail or in camp! Learn More
Mac King's Campfire Magic$12.95When a magic book starts with a foreword by Las Vegas headlining illusionists Penn & Teller, how can you go wrong? This book's subtitle says it all: "50 Amazing, Easy-to-Learn Tricks and Mind-Blowing Stunts Using Cards, String, Pencils, and Other Stuff from Your Knapsack." Learn More